Spontaneous Fusion with Transformed Mesenchymal Stromal Cells Results in Complete Heterogeneity in Prostate Cancer Cells
Tumor cells gain advantages in growth and survival by acquiring genotypic and phenotypic heterogeneity. Interactions with bystander cells in the tumor microenvironment contribute to the progression of heterogeneity. We have shown that fusion between tumor and bystander cells is one form of interacti...
| Main Authors: | , , , , , , , , , , |
|---|---|
| Format: | Article |
| Language: | English |
| Published: |
MDPI AG
2024-02-01
|
| Series: | Cancers |
| Subjects: | |
| Online Access: | https://www.mdpi.com/2072-6694/16/5/951 |
| _version_ | 1797264737125269504 |
|---|---|
| author | Ruoxiang Wang Peizhen Hu Fubo Wang Ji Lyu Yan Ou Mouad Edderkaoui Yi Zhang Michael S. Lewis Stephen J. Pandol Haiyen E. Zhau Leland W. K. Chung |
| author_facet | Ruoxiang Wang Peizhen Hu Fubo Wang Ji Lyu Yan Ou Mouad Edderkaoui Yi Zhang Michael S. Lewis Stephen J. Pandol Haiyen E. Zhau Leland W. K. Chung |
| author_sort | Ruoxiang Wang |
| collection | DOAJ |
| description | Tumor cells gain advantages in growth and survival by acquiring genotypic and phenotypic heterogeneity. Interactions with bystander cells in the tumor microenvironment contribute to the progression of heterogeneity. We have shown that fusion between tumor and bystander cells is one form of interaction, and that tumor–bystander cell fusion has contrasting effects. By trapping fusion hybrids in the heterokaryon or synkaryon state, tumor–bystander cell fusion prevents the progression of heterogeneity. However, if trapping fails, fusion hybrids will resume replication to form derivative clones with diverse genomic makeups and behavioral phenotypes. To determine the characteristics of bystander cells that influence the fate of fusion hybrids, we co-cultured prostate mesenchymal stromal cell lines and their spontaneously transformed sublines with LNCaP as well as HPE-15 prostate cancer cells. Subclones derived from cancer–stromal fusion hybrids were examined for genotypic and phenotypic diversifications. Both stromal cell lines were capable of fusing with cancer cells, but only fusion hybrids with the transformed stromal subline generated large numbers of derivative subclones. Each subclone had distinct cell morphologies and growth behaviors and was detected with complete genomic hybridization. The health conditions of the bystander cell compartment play a crucial role in the progression of tumor cell heterogeneity. |
| first_indexed | 2024-04-25T00:33:39Z |
| format | Article |
| id | doaj.art-b8a2d1db61ca4a89abc0df342971134b |
| institution | Directory Open Access Journal |
| issn | 2072-6694 |
| language | English |
| last_indexed | 2024-04-25T00:33:39Z |
| publishDate | 2024-02-01 |
| publisher | MDPI AG |
| record_format | Article |
| series | Cancers |
| spelling | doaj.art-b8a2d1db61ca4a89abc0df342971134b2024-03-12T16:40:57ZengMDPI AGCancers2072-66942024-02-0116595110.3390/cancers16050951Spontaneous Fusion with Transformed Mesenchymal Stromal Cells Results in Complete Heterogeneity in Prostate Cancer CellsRuoxiang Wang0Peizhen Hu1Fubo Wang2Ji Lyu3Yan Ou4Mouad Edderkaoui5Yi Zhang6Michael S. Lewis7Stephen J. Pandol8Haiyen E. Zhau9Leland W. K. Chung10Department of Medicine, Cedars-Sinai Medical Center, Los Angeles, CA 90048, USADepartment of Medicine, Cedars-Sinai Medical Center, Los Angeles, CA 90048, USADepartment of Medicine, Cedars-Sinai Medical Center, Los Angeles, CA 90048, USADepartment of Medicine, Cedars-Sinai Medical Center, Los Angeles, CA 90048, USADepartment of Biomedical Sciences, Cedars-Sinai Medical Center, Los Angeles, CA 90048, USADepartment of Medicine, Cedars-Sinai Medical Center, Los Angeles, CA 90048, USADepartment of Biomedical Sciences, Cedars-Sinai Medical Center, Los Angeles, CA 90048, USADepartment of Medicine and Pathology, Cedars-Sinai Medical Center, Los Angeles, CA 90048, USADepartment of Medicine, Cedars-Sinai Medical Center, Los Angeles, CA 90048, USADepartment of Medicine, Cedars-Sinai Medical Center, Los Angeles, CA 90048, USADepartment of Medicine, Cedars-Sinai Medical Center, Los Angeles, CA 90048, USATumor cells gain advantages in growth and survival by acquiring genotypic and phenotypic heterogeneity. Interactions with bystander cells in the tumor microenvironment contribute to the progression of heterogeneity. We have shown that fusion between tumor and bystander cells is one form of interaction, and that tumor–bystander cell fusion has contrasting effects. By trapping fusion hybrids in the heterokaryon or synkaryon state, tumor–bystander cell fusion prevents the progression of heterogeneity. However, if trapping fails, fusion hybrids will resume replication to form derivative clones with diverse genomic makeups and behavioral phenotypes. To determine the characteristics of bystander cells that influence the fate of fusion hybrids, we co-cultured prostate mesenchymal stromal cell lines and their spontaneously transformed sublines with LNCaP as well as HPE-15 prostate cancer cells. Subclones derived from cancer–stromal fusion hybrids were examined for genotypic and phenotypic diversifications. Both stromal cell lines were capable of fusing with cancer cells, but only fusion hybrids with the transformed stromal subline generated large numbers of derivative subclones. Each subclone had distinct cell morphologies and growth behaviors and was detected with complete genomic hybridization. The health conditions of the bystander cell compartment play a crucial role in the progression of tumor cell heterogeneity.https://www.mdpi.com/2072-6694/16/5/951tumor cellsbystander cellsstromal cell transformationcell fusioncancer–stromal hybridizationheterogeneity progression |
| spellingShingle | Ruoxiang Wang Peizhen Hu Fubo Wang Ji Lyu Yan Ou Mouad Edderkaoui Yi Zhang Michael S. Lewis Stephen J. Pandol Haiyen E. Zhau Leland W. K. Chung Spontaneous Fusion with Transformed Mesenchymal Stromal Cells Results in Complete Heterogeneity in Prostate Cancer Cells Cancers tumor cells bystander cells stromal cell transformation cell fusion cancer–stromal hybridization heterogeneity progression |
| title | Spontaneous Fusion with Transformed Mesenchymal Stromal Cells Results in Complete Heterogeneity in Prostate Cancer Cells |
| title_full | Spontaneous Fusion with Transformed Mesenchymal Stromal Cells Results in Complete Heterogeneity in Prostate Cancer Cells |
| title_fullStr | Spontaneous Fusion with Transformed Mesenchymal Stromal Cells Results in Complete Heterogeneity in Prostate Cancer Cells |
| title_full_unstemmed | Spontaneous Fusion with Transformed Mesenchymal Stromal Cells Results in Complete Heterogeneity in Prostate Cancer Cells |
| title_short | Spontaneous Fusion with Transformed Mesenchymal Stromal Cells Results in Complete Heterogeneity in Prostate Cancer Cells |
| title_sort | spontaneous fusion with transformed mesenchymal stromal cells results in complete heterogeneity in prostate cancer cells |
| topic | tumor cells bystander cells stromal cell transformation cell fusion cancer–stromal hybridization heterogeneity progression |
| url | https://www.mdpi.com/2072-6694/16/5/951 |
| work_keys_str_mv | AT ruoxiangwang spontaneousfusionwithtransformedmesenchymalstromalcellsresultsincompleteheterogeneityinprostatecancercells AT peizhenhu spontaneousfusionwithtransformedmesenchymalstromalcellsresultsincompleteheterogeneityinprostatecancercells AT fubowang spontaneousfusionwithtransformedmesenchymalstromalcellsresultsincompleteheterogeneityinprostatecancercells AT jilyu spontaneousfusionwithtransformedmesenchymalstromalcellsresultsincompleteheterogeneityinprostatecancercells AT yanou spontaneousfusionwithtransformedmesenchymalstromalcellsresultsincompleteheterogeneityinprostatecancercells AT mouadedderkaoui spontaneousfusionwithtransformedmesenchymalstromalcellsresultsincompleteheterogeneityinprostatecancercells AT yizhang spontaneousfusionwithtransformedmesenchymalstromalcellsresultsincompleteheterogeneityinprostatecancercells AT michaelslewis spontaneousfusionwithtransformedmesenchymalstromalcellsresultsincompleteheterogeneityinprostatecancercells AT stephenjpandol spontaneousfusionwithtransformedmesenchymalstromalcellsresultsincompleteheterogeneityinprostatecancercells AT haiyenezhau spontaneousfusionwithtransformedmesenchymalstromalcellsresultsincompleteheterogeneityinprostatecancercells AT lelandwkchung spontaneousfusionwithtransformedmesenchymalstromalcellsresultsincompleteheterogeneityinprostatecancercells |